Gisondi 2008.

Study characteristics
Methods	RCT, active‐controlled, investigator‐blinded pilot trial Date of study: February 2002 ‐ February 2005 Location: Verona, Italy
Participants	Randomised: 60 participants (mean age 55 years (acitretin); 55 years (etanercept), 53 years (acitretin + etanercept), 33 male) Inclusion criteria Participants with moderate‐severe psoriasis Age ≥ 18 Exclusion criteria Fertile women, kidney insufficiency (severe disorder), liver insufficiency (severe disorder) Had received biologics Had an active infection (HIV, Hepatitis B & C, latent TB) Had demyelinating diseases Has uncontrolled cardiovascular disorder (severe heart failure) Had past history of malignant tumours Dropouts and withdrawals 4/60 (6.6%): acitretin group (4), etanercept group (0), acitretin + etanercept group (0) Inefficacy of the treatment: acitretin group (4)
Interventions	Intervention A. Etanercept (25 mg) and acitretin (0.4 mg/kg) (n = 18), SC (etanercept) and orally (acitretin), twice a week (etanercept) and once a day (acitretin), 24 weeks Control intervention B. Acitretin (n = 20), orally, 0.4 mg/kg, once a day, 24 weeks C. Etanercept (n = 22), SC, 25 mg, twice a week, 24 weeks
Outcomes	Assessments at 24 weeks Primary outcomes of the trial ≥ PASI 75 improvement from baseline Secondary outcomes of the trial PASI 50 BSA Number of participants reporting significant changes (e.g. > 3 times the normal value for AST and ALT and > double the normal value for cholesterol and triglycerides)
Notes	Funding: not stated Declarations of interest (p 1345): "PG has received lecture fees from Merck‐Serono, Schering‐Plough, Wyeth. GG has received consultation and lecture fees from Abbott, Janssen‐Cilag, Merck‐Serono, Schering‐Plough, Wyeth."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 1346): "Randomization was performed with the use of computer‐generated random numbers and block size of four patients" Comment: probably done
Allocation concealment (selection bias)	Unclear risk	Quote (p 1346): "Randomization was performed with the use of computer‐generated random numbers and block size of four patients" Comment: no description of the method used to guarantee allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: not blinded
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote (p 1346): "The PASI assessor was blinded concerning the group allocation of the patient" Comment: acitretin provide visible AEs
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Randomly assigned 60, analysed 60 Management of missing data, quote (p 1346): "An ITT analysis was performed" Comment: no description of the method used to manage the missing data
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol was available. The prespecified outcomes mentioned in the Methods section appeared to have been reported